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The hypotensive effect of intrathecally injected (m)VD-hemopressin(α) in urethane-anesthetized rats.
Peptides. 2014 Jun; 56:45-51.P

Abstract

Previous studies suggest that cannabinoids system plays an important role in cardiovascular regulation. (m)VD-hemopressin(α) (VD-Hpα), an 11-residue peptide originating from the α1 chain of hemoglobin, was recently reported as a selective agonist of cannabinoid CB1 receptor. The present study was undertaken to investigate the intrathecal (i.t.) action of (m)VD-Hpα on blood pressure in urethane-anesthetized rats. Our results demonstrated that injections of (m)VD-Hpα (5-30 nmol, i.t.) produced a dose-dependent decrease in mean arterial pressure (MAP), similar to that of the non-peptidic cannabinoid receptor agonist WIN55212-2 (1.25-10 nmol, i.t.). The hypotensive effect of (m)VD-Hpα was not influenced by the CB1 receptor antagonist AM251 (20 nmol, i.t.) or the CB2 receptor antagonist AM630 (20 nmol, i.t.). However, WIN55212-2-induced hypotension was almost completely prevented by i.t. administration of AM251, not by AM630. The spinal hypotension of (m)VD-Hpα and WIN55212-2 was significantly reduced by pretreatment with the α-adrenoceptor antagonist phentolamine (1 mg/kg, i.v.), but not by the β-adrenoceptor antagonist propranolol (2 mg/kg, i.v.) or the muscarinic receptor antagonist atropine (2 mg/kg, i.v.). In addition, L-NAME (50 mg/kg, i.v.), the inhibitor of nitric oxide (NO) synthase, significantly reduced WIN55212-2-induced hypotension, but had no effect on the hypotensive response to (m)VD-Hpα. Collectively, the results show that i.t. administration of (m)VD-Hpα induces a decrease in MAP via a non-CB1 and non-CB2 mechanism.

Authors+Show Affiliations

Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China. Electronic address: wangrui@lzu.edu.cn.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China. Electronic address: fangq@lzu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24681436

Citation

Li, Xu-hui, et al. "The Hypotensive Effect of Intrathecally Injected (m)VD-hemopressin(α) in Urethane-anesthetized Rats." Peptides, vol. 56, 2014, pp. 45-51.
Li XH, Li N, Wang ZL, et al. The hypotensive effect of intrathecally injected (m)VD-hemopressin(α) in urethane-anesthetized rats. Peptides. 2014;56:45-51.
Li, X. H., Li, N., Wang, Z. L., Pan, J. X., Han, Z. L., Chang, X. M., Tang, H. H., Wang, P., Wang, R., & Fang, Q. (2014). The hypotensive effect of intrathecally injected (m)VD-hemopressin(α) in urethane-anesthetized rats. Peptides, 56, 45-51. https://doi.org/10.1016/j.peptides.2014.03.012
Li XH, et al. The Hypotensive Effect of Intrathecally Injected (m)VD-hemopressin(α) in Urethane-anesthetized Rats. Peptides. 2014;56:45-51. PubMed PMID: 24681436.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The hypotensive effect of intrathecally injected (m)VD-hemopressin(α) in urethane-anesthetized rats. AU - Li,Xu-hui, AU - Li,Ning, AU - Wang,Zi-long, AU - Pan,Jia-xin, AU - Han,Zheng-lan, AU - Chang,Xue-mei, AU - Tang,Hong-hai, AU - Wang,Pei, AU - Wang,Rui, AU - Fang,Quan, Y1 - 2014/03/26/ PY - 2014/01/15/received PY - 2014/03/17/revised PY - 2014/03/17/accepted PY - 2014/4/1/entrez PY - 2014/4/1/pubmed PY - 2015/1/13/medline KW - (m)VD-hemopressin(α) KW - Antagonist KW - Cannabinoid KW - Hypotensive response KW - Rat SP - 45 EP - 51 JF - Peptides JO - Peptides VL - 56 N2 - Previous studies suggest that cannabinoids system plays an important role in cardiovascular regulation. (m)VD-hemopressin(α) (VD-Hpα), an 11-residue peptide originating from the α1 chain of hemoglobin, was recently reported as a selective agonist of cannabinoid CB1 receptor. The present study was undertaken to investigate the intrathecal (i.t.) action of (m)VD-Hpα on blood pressure in urethane-anesthetized rats. Our results demonstrated that injections of (m)VD-Hpα (5-30 nmol, i.t.) produced a dose-dependent decrease in mean arterial pressure (MAP), similar to that of the non-peptidic cannabinoid receptor agonist WIN55212-2 (1.25-10 nmol, i.t.). The hypotensive effect of (m)VD-Hpα was not influenced by the CB1 receptor antagonist AM251 (20 nmol, i.t.) or the CB2 receptor antagonist AM630 (20 nmol, i.t.). However, WIN55212-2-induced hypotension was almost completely prevented by i.t. administration of AM251, not by AM630. The spinal hypotension of (m)VD-Hpα and WIN55212-2 was significantly reduced by pretreatment with the α-adrenoceptor antagonist phentolamine (1 mg/kg, i.v.), but not by the β-adrenoceptor antagonist propranolol (2 mg/kg, i.v.) or the muscarinic receptor antagonist atropine (2 mg/kg, i.v.). In addition, L-NAME (50 mg/kg, i.v.), the inhibitor of nitric oxide (NO) synthase, significantly reduced WIN55212-2-induced hypotension, but had no effect on the hypotensive response to (m)VD-Hpα. Collectively, the results show that i.t. administration of (m)VD-Hpα induces a decrease in MAP via a non-CB1 and non-CB2 mechanism. SN - 1873-5169 UR - https://www.unboundmedicine.com/medline/citation/24681436/The_hypotensive_effect_of_intrathecally_injected__m_VD_hemopressin_α__in_urethane_anesthetized_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0196-9781(14)00088-6 DB - PRIME DP - Unbound Medicine ER -